Risk factors for Gram-negative bacterial bloodstream infections: a systematic review and meta-analysis with subgroup analyses for carbapenem-resistant organisms and Acinetobacter baumannii

Abstract

Abstract Background Gram-negative bacterial (GNB) bloodstream infections (BSIs), particularly those caused by carbapenem-resistant GNB (CR-GNB) and Acinetobacter baumannii (AB), are associated with substantial morbidity and mortality. This study aimed to provide, to our knowledge, the first comprehensive meta-analysis integrating overall GNB-BSI risk factors with both pathogen-specific and resistance-defined subgroup analyses. Methods A systematic literature search was conducted across PubMed, Web of Science, Embase, the Cochrane Library, and four major Chinese databases from inception to August 2025. We included observational studies evaluating risk factors for GNB-related BSIs in patients with GNB infections. Two reviewers independently performed study screening, data extraction, and quality assessment. Methodological quality was evaluated using the Newcastle–Ottawa Scale and the Agency for Healthcare Research and Quality tool. Meta-analyses were performed using R software. Pooled odds ratios (ORs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated using the Mantel-Haenszel method, applying either fixed-effects or random-effects models based on the degree of heterogeneity. Furthermore, pre-specified subgroup analyses were conducted to explore potential sources of heterogeneity. Results Seventy-five studies (76 articles), encompassing 26,377 patients with GNB infections, were included. The pooled incidence of BSI was 17.3%. Of the 29 evaluated risk factors, 17 were significantly associated with GNB-BSI in the overall population. Procalcitonin (SMD, 0.64; 95%CI, 0.39–0.88), C-reactive protein (SMD, 0.63; 95%CI, 0.43–0.83), carbapenem use (OR, 2.49; 95%CI, 1.92–3.23), mechanical ventilation (OR, 2.51; 95%CI, 1.74–3.61), central venous catheterization (OR, 2.67; 95%CI, 2.27–3.15), immunosuppressive status (OR, 2.20; 95%CI, 1.50–3.22), and aminoglycoside use (OR, 1.68; 95%CI, 1.31–2.15) emerged as the most consistent risk predictors of GNB-BSI. Subgroup analyses indicated that CR-GNB–BSI was specifically associated with hypoalbuminemia and indwelling urinary catheter use, whereas continuous renal replacement therapy was uniquely associated with AB-BSI. Conclusions As the first meta-analysis to integrate pathogen-specific and resistance-defined subgroups, this study delineates distinct risk profiles for GNB-BSI. While biomarkers of inflammation, prior carbapenem exposure, and invasive procedures represent broadly shared predictors, CR-GNB–BSI and AB-BSI exhibit additional, subtype-specific risk factors. These findings assist clinicians in the early identification of BSIs among patients with GNB infections. Registration number CRD420251117325. Clinical trial number Not applicable.